On the Stress-Strength Reliability of Transmuted GEV Random Variables with Applications to Financial Assets Selection.

In reliability contexts, probabilities of the type R=P(X

Discovery of Delirium Biomarkers through Minimally Invasive Serum Molecular Fingerprinting.

Delirium presents a significant clinical challenge, primarily due to its profound impact on patient outcomes and the limitations of the current diagnostic methods, which are largely subjective. During the COVID-19 pandemic, this challenge was intensified as the frequency of delirium assessments decreased in Intensive Care Units (ICUs), even as the prevalence of delirium among critically ill patients increased. The present study evaluated how the serum molecular fingerprint, as acquired by Fourier-Transform InfraRed (FTIR) spectroscopy, can enable the development of predictive models for delirium. A preliminary univariate analysis of serum FTIR spectra indicated significantly different bands between 26 ICU patients with delirium and 26 patients without, all of whom were admitted with COVID-19. However, these bands resulted in a poorly performing Naïve-Bayes predictive model. Considering the use of a Fast-Correlation-Based Filter for feature selection, it was possible to define a new set of spectral bands with a wider coverage of molecular functional groups. These bands ensured an excellent Naïve-Bayes predictive model, with an AUC, a sensitivity, and a specificity all exceeding 0.92. These spectral bands, acquired through a minimally invasive analysis and obtained rapidly, economically, and in a high-throughput mode, therefore offer significant potential for managing delirium in critically ill patients.

A new methodology for a rapid and high-throughput comparison of molecular profiles and biological activity of phytoextracts.

To robustly discover and explore phytocompounds, it is necessary to evaluate the interrelationships between the plant species, plant tissue, and the extraction process on the extract composition and to predict its cytotoxicity. The present work evaluated how Fourier Transform InfraRed spectroscopy can acquire the molecular profile of aqueous and ethanol-based extracts obtained from leaves, seeds, and flowers of Cynara Cardunculus, and ethanol-based extracts from Matricaria chamomilla flowers, as well the impact of these extracts on the viability of mammalian cells. The extract molecular profile enabled to predict the extraction yield, and how the plant species, plant tissue, and extraction process affected the extract's relative composition. The molecular profile obtained from the culture media of cells exposed to extracts enabled to capture its impact on cells metabolism, at a higher sensitivity than the conventional assay used to determine the cell viability. Furthermore, it was possible to detect specific impacts on the cell's metabolism according to plant species, plant tissue, and extraction process. Since spectra were acquired on small volumes of samples (25 µL), after a simple dehydration step, and based on a plate with 96 wells, the method can be applied in a rapid, simple, high-throughput, and economic mode, consequently promoting the discovery of phytocompounds.

Simplifying Data Analysis in Biomedical Research: An Automated, User-Friendly Tool.

Robust data normalization and analysis are pivotal in biomedical research to ensure that observed differences in populations are directly attributable to the target variable, rather than disparities between control and study groups. ArsHive addresses this challenge using advanced algorithms to normalize populations (e.g., control and study groups) and perform statistical evaluations between demographic, clinical, and other variables within biomedical datasets, resulting in more balanced and unbiased analyses. The tool's functionality extends to comprehensive data reporting, which elucidates the effects of data processing, while maintaining dataset integrity. Additionally, ArsHive is complemented by A.D.A. (Autonomous Digital Assistant), which employs OpenAI's GPT-4 model to assist researchers with inquiries, enhancing the decision-making process. In this proof-of-concept study, we tested ArsHive on three different datasets derived from proprietary data, demonstrating its effectiveness in managing complex clinical and therapeutic information and highlighting its versatility for diverse research fields.

Loss of Dnmt3a increases self-renewal and resistance to pegIFN-α in JAK2-V617F-positive myeloproliferative neoplasms.

ABSTRACT: Pegylated interferon alfa (pegIFN-α) can induce molecular remissions in patients with JAK2-V617F-positive myeloproliferative neoplasms (MPNs) by targeting long-term hematopoietic stem cells (LT-HSCs). Additional somatic mutations in genes regulating LT-HSC self-renewal, such as DNMT3A, have been reported to have poorer responses to pegIFN-α. We investigated whether DNMT3A loss leads to alterations in JAK2-V617F LT-HSC functions conferring resistance to pegIFN-α treatment in a mouse model of MPN and in hematopoietic progenitors from patients with MPN. Long-term treatment with pegIFN-α normalized blood parameters and reduced splenomegaly and JAK2-V617F chimerism in single-mutant JAK2-V617F (VF) mice. However, pegIFN-α in VF;Dnmt3aΔ/Δ (VF;DmΔ/Δ) mice worsened splenomegaly and failed to reduce JAK2-V617F chimerism. Furthermore, LT-HSCs from VF;DmΔ/Δ mice compared with VF were less prone to accumulate DNA damage and exit dormancy upon pegIFN-α treatment. RNA sequencing showed that IFN-α induced stronger upregulation of inflammatory pathways in LT-HSCs from VF;DmΔ/Δ than from VF mice, indicating that the resistance of VF;DmΔ/Δ LT-HSC was not due to failure in IFN-α signaling. Transplantations of bone marrow from pegIFN-α-treated VF;DmΔ/Δ mice gave rise to more aggressive disease in secondary and tertiary recipients. Liquid cultures of hematopoietic progenitors from patients with MPN with JAK2-V617F and DNMT3A mutation showed increased percentages of JAK2-V617F-positive colonies upon IFN-α exposure, whereas in patients with JAK2-V617F alone, the percentages of JAK2-V617F-positive colonies decreased or remained unchanged. PegIFN-α combined with 5-azacytidine only partially overcame resistance in VF;DmΔ/Δ mice. However, this combination strongly decreased the JAK2-mutant allele burden in mice carrying VF mutation only, showing potential to inflict substantial damage preferentially to the JAK2-mutant clone.

Inherited Metabolic Disorders: From Bench to Bedside.

Inherited metabolic disorders (IMDs), commonly referred to as inborn errors of metabolism, represent a spectrum of disorders with a defined (or presumed) primary genetic cause which disrupts the normal metabolism of essential molecules in the body [...].

The glutaminase inhibitor CB-839 targets metabolic dependencies of JAK2-mutant hematopoiesis in MPN.

ABSTRACT: Hyperproliferation of myeloid and erythroid cells in myeloproliferative neoplasms (MPN) driven by the JAK2-V617F mutation is associated with altered metabolism. Given the central role of glutamine in anabolic and catabolic pathways, we examined the effects of pharmacologically inhibiting glutaminolysis, that is, the conversion of glutamine (Gln) to glutamate (Glu), using CB-839, a small molecular inhibitor of the enzyme glutaminase (GLS). We show that CB-839 strongly reduced the mitochondrial respiration rate of bone marrow cells from JAK2-V617F mutant (VF) mice, demonstrating a marked dependence of these cells on Gln-derived ATP production. Consistently, in vivo treatment with CB-839 normalized blood glucose levels, reduced splenomegaly and decreased erythrocytosis in VF mice. These effects were more pronounced when CB-839 was combined with the JAK1/2 inhibitor ruxolitinib or the glycolysis inhibitor 3PO, indicating possible synergies when cotargeting different metabolic and oncogenic pathways. Furthermore, we show that the inhibition of glutaminolysis with CB-839 preferentially lowered the proportion of JAK2-mutant hematopoietic stem cells (HSCs). The total number of HSCs was decreased by CB-839, primarily by reducing HSCs in the G1 phase of the cell cycle. CB-839 in combination with ruxolitinib also strongly reduced myelofibrosis at later stages of MPN. In line with the effects shown in mice, proliferation of CD34+ hematopoietic stem and progenitor cells from polycythemia vera patients was inhibited by CB-839 at nanomolar concentrations. These data suggest that inhibiting GLS alone or in combination with inhibitors of glycolysis or JAK2 inhibitors represents an attractive new therapeutic approach to MPN.

The Impact of the Serum Extraction Protocol on Metabolomic Profiling Using UPLC-MS/MS and FTIR Spectroscopy.

Biofluid metabolomics is a very appealing tool to increase the knowledge associated with pathophysiological mechanisms leading to better and new therapies and biomarkers for disease diagnosis and prognosis. However, due to the complex process of metabolome analysis, including the metabolome isolation method and the platform used to analyze it, there are diverse factors that affect metabolomics output. In the present work, the impact of two protocols to extract the serum metabolome, one using methanol and another using a mixture of methanol, acetonitrile, and water, was evaluated. The metabolome was analyzed by ultraperformance liquid chromatography associated with tandem mass spectrometry (UPLC-MS/MS), based on reverse-phase and hydrophobic chromatographic separations, and Fourier transform infrared (FTIR) spectroscopy. The two extraction protocols of the metabolome were compared over the analytical platforms (UPLC-MS/MS and FTIR spectroscopy) concerning the number of features, the type of features, common features, and the reproducibility of extraction replicas and analytical replicas. The ability of the extraction protocols to predict the survivability of critically ill patients hospitalized at an intensive care unit was also evaluated. The FTIR spectroscopy platform was compared to the UPLC-MS/MS platform and, despite not identifying metabolites and consequently not contributing as much as UPLC-MS/MS in terms of information concerning metabolic information, it enabled the comparison of the two extraction protocols as well as the development of very good predictive models of patient's survivability, such as the UPLC-MS/MS platform. Furthermore, FTIR spectroscopy is based on much simpler procedures and is rapid, economic, and applicable in the high-throughput mode, i.e., enabling the simultaneous analysis of hundreds of samples in the microliter range in a couple of hours. Therefore, FTIR spectroscopy represents a very interesting complementary technique not only to optimize processes as the metabolome isolation but also for obtaining biomarkers such as those for disease prognosis.

Impact of Clonal Architecture on Clinical Course and Prognosis in Patients With Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are caused by a somatic gain-of-function mutation in 1 of the 3 disease driver genes JAK2, MPL, or CALR. About half of the MPNs patients also carry additional somatic mutations that modify the clinical course. The order of acquisition of these gene mutations has been proposed to influence the phenotype and evolution of the disease. We studied 50 JAK2-V617F-positive MPN patients who carried at least 1 additional somatic mutation and determined the clonal architecture of their hematopoiesis by sequencing DNA from single-cell-derived colonies. In 22 of these patients, the same blood samples were also studied for comparison by Tapestri single-cell DNA sequencing (scDNAseq). The clonal architectures derived by the 2 methods showed good overall concordance. scDNAseq showed higher sensitivity for mutations with low variant allele fraction, but had more difficulties distinguishing between heterozygous and homozygous mutations. By unsupervised analysis of clonal architecture data from all 50 MPN patients, we defined 4 distinct clusters. Cluster 4, characterized by more complex subclonal structure correlated with reduced overall survival, independent of the MPN subtype, presence of high molecular risk mutations, or the age at diagnosis. Cluster 1 was characterized by additional mutations residing in clones separated from the JAK2-V617F clone. The correlation with overall survival improved when mutation in such separated clones were not counted. Our results show that scDNAseq can reliably decipher the clonal architecture and can be used to refine the molecular prognostic stratification that until now was primarily based on the clinical and laboratory parameters.

Influence of Ethanol Parametrization on Diffusion Coefficients Using OPLS-AA Force Field.

Molecular dynamics simulations employing the all-atom optimized potential for liquid simulations (OPLS-AA) force field were performed for determining self-diffusion coefficients (D11) of ethanol and tracer diffusion coefficients (D12) of solutes in ethanol at several temperature and pressure conditions. For simulations employing the original OPLS-AA diameter of ethanol's oxygen atom (σOH), calculated and experimental diffusivities of protic solutes differed by more than 25%. To correct this behavior, the σOH was reoptimized using the experimental D12 of quercetin and of gallic acid in liquid ethanol as benchmarks. A substantial improvement of the calculated diffusivities was found by changing σOH from its original value (0.312 nm) to 0.306 nm, with average absolute relative deviations (AARD) of 3.71% and 4.59% for quercetin and gallic acid, respectively. The new σOH value was further tested by computing D12 of ibuprofen and butan-1-ol in liquid ethanol with AARDs of 1.55% and 4.81%, respectively. A significant improvement was also obtained for the D11 of ethanol with AARD = 3.51%. It was also demonstrated that in the case of diffusion coefficients of non-polar solutes in ethanol, the original σOH=0.312 nm should be used for better agreement with experiment. If equilibrium properties such as enthalpy of vaporization and density are estimated, the original diameter should be once again adopted.

Dataset for identifying maintenance needs of home appliances using artificial intelligence.

The ability to predict the maintenance needs of machines is generating increasing interest in a wide range of industries as it contributes to diminishing machine downtime and costs while increasing efficiency when compared to traditional maintenance approaches. Predictive maintenance (PdM) methods, based on state-of-the-art Internet of Things (IoT) systems and Artificial Intelligence (AI) techniques, are heavily dependent on data to create analytical models capable of identifying certain patterns which can represent a malfunction or deterioration in the monitored machines. Therefore, a realistic and representative dataset is paramount for creating, training, and validating PdM techniques. This paper introduces a new dataset, which integrates real-world data from home appliances, such as refrigerators and washing machines, suitable for the development and testing of PdM algorithms. The data was collected on various home appliances at a repair center and included readings of electrical current and vibration at low (1 Hz) and high (2048 Hz) sampling frequencies. The dataset samples are filtered and tagged with both normal and malfunction types. An extracted features dataset, corresponding to the collected working cycles is also made available. This dataset could benefit research and development of AI systems for home appliances' predictive maintenance tasks and outlier detection analysis. The dataset can also be repurposed for smart-grid or smart-home applications, predicting the consumption patterns of such home appliances.

The Characteristics and Laboratory Findings of SARS-CoV-2 Infected Patients during the First Three COVID-19 Waves in Portugal-A Retrospective Single-Center Study.

Background and Objectives: Given the wide spectrum of clinical and laboratory manifestations of the coronavirus disease 2019 (COVID-19), it is imperative to identify potential contributing factors to patients' outcomes. However, a limited number of studies have assessed how the different waves affected the progression of the disease, more so in Portugal. Therefore, our main purpose was to study the clinical and laboratory patterns of COVID-19 in an unvaccinated population admitted to the intensive care unit, identifying characteristics associated with death, in each of the first three waves of the pandemic. Materials and Methods: This study included 337 COVID-19 patients admitted to the intensive care unit of a single-center hospital in Lisbon, Portugal, between March 2020 and March 2021. Comparisons were made between three COVID-19 waves, in the second (n = 325) and seventh (n = 216) days after admission, and between discharged and deceased patients. Results: Deceased patients were considerably older (p = 0.021) and needed greater ventilatory assistance (p = 0.023), especially in the first wave. Differences between discharged and deceased patients' biomarkers were minimal in the first wave, on both analyzed days. In the second wave significant differences emerged in troponins, lactate dehydrogenase, procalcitonin, C-reactive protein, and white blood cell subpopulations, as well as platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios (all p < 0.05). Furthermore, in the third wave, platelets and D-dimers were also significantly different between patients' groups (all p < 0.05). From the second to the seventh days, troponins and lactate dehydrogenase showed significant decreases, mainly for discharged patients, while platelet counts increased (all p < 0.01). Lymphocytes significantly increased in discharged patients (all p < 0.05), while white blood cells rose in the second (all p < 0.001) and third (all p < 0.05) waves among deceased patients. Conclusions: This study yields insights into COVID-19 patients' characteristics and mortality-associated biomarkers during Portugal's first three COVID-19 waves, highlighting the importance of considering wave variations in future research due to potential significant outcome differences.

Predictors of in-hospital mortality in critically ill patients with COVID-19: a large dual tertiary centre study.

OBJECTIVES: The aim of this study was to investigate the relationship of echocardiographic parameters, laboratory findings and clinical characteristics with in-hospital mortality in adult patients with COVID-19 admitted to the intensive care units (ICU) in two large collaborating tertiary UK centres. DESIGN: Observational retrospective study. SETTING: The study was conducted in patients admitted to the ICU in two large tertiary centres in London, UK. PARTICIPANTS: Inclusion criteria were: (1) patients admitted to the ICU with a COVID-19 diagnosis over a period of 16 weeks. and (2) underwent a transthoracic echocardiogram on the first day of ICU admission as clinically indicated.No exclusion criteria applied.Three hundred patients were enrolled and completed the follow-up. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure in this study was in-hospital mortality in patients admitted to the ICU with COVID-19 infection. RESULTS: Older age (HR: 1.027, 95% CI 1.007 to 1.047; p=0.008), left ventricular (LV) ejection fraction<35% (HR: 5.908, 95% CI 2.609 to 13.376; p<0.001), and peak C reactive protein (CRP) (HR: 1.002, 95% CI 1.001 to 1.004, p=0.001) were independently correlated with mortality in a multivariable Cox regression model. Following multiple imputation of variables with more than 5% missing values, random forest analysis was applied to the imputed data. Right ventricular (RV) basal diameter (RVD1), RV mid-cavity diameter (RVD2), tricuspid annular plane systolic excursion, RV systolic pressure, hypertension, RV dysfunction, troponin level on admission, peak CRP, creatinine level on ICU admission, body mass index and age were found to have a high relative importance (> 0.7). CONCLUSIONS: In patients with COVID-19 in the ICU, both severely impaired LV function and impaired RV function may have adverse prognostic implications, but older age and inflammatory markers appear to have a greater impact. A combination of echocardiographic and laboratory investigations as well as demographic and clinical characteristics appears appropriate for risk stratification in patients with COVID-19 who are admitted to the ICU.

Alterações no fluxo de atendimento a pacientes em quimioterapia: relato de atendimento durante pandemia covid-19 / Changes in the flow of care for patients undergoing chemotherapy: report of care during pandemic covid-19 / Cambios en el flujo de atención para pacientes sometidos a quimioterapia: informe de atención durante la pandemia covid-19

Objetivo: Analisar as modificações no fluxo de atendimento aos pacientes oncológicos, perante a pandemia de COVID-19. Métodos: Trata-se de uma pesquisa documental em um ambulatório privado de Aracaju, sendo inclusas as orientações das bases disponibilizados pelo Ministério da Saúde, pelo Instituto Nacional de Câncer e pelo Departamento de Informática do SUS (DATASUS), referentes ao SubSistema de Informações Hospitalares (SIH), bem como os dados do Sistema de Informações Ambulatoriais do SUS (SIA-SUS), módulo de alta complexidade para atendimento oncológico (APAC/ONCO). Resultados: O fluxo dos pacientes na entrada do ambulatório inicia com a identificação dos sinais de síndrome gripal. Após a higienização das mãos e aferição da temperatura, há direcionamento a outro ambiente com a distancia mínima de um metro entre as pessoas, sobre uso indispensável de máscara. Caso o paciente seja suspeito, deve mantê-lo em área separada e priorizar o seu atendimento. Conclusão: Foram observadas as principais orientações que devem existir no fluxo de entrada ambulatorial aos pacientes oncológicos, devido à necessidade de reavaliação das prioridades de atendimento e de reorganização a logística de trabalho, com a pandemia do COVID-19. (AU)

Objective: To analyze changes in the flow of care for cancer patients, in the face of COVID-19 pandemic. Methods: This is a documentary research in a private outpatient clinic in Aracaju, including the guidelines provided by the Ministry of Health, the National Cancer Institute and the SUS Computer Department (DATASUS), referring to the Hospital Information SubSystem. (SIH), as well as data from the SUS Outpatient Information System (SIA-SUS), a highly complex module for cancer care (APAC / ONCO). Results: The flow of patients at the entrance to the clinic begins with the identification of signs of flu syndrome. After hand hygiene and temperature measurement, there is a direction to another environment with a minimum distance of 1 meter between people, about the indispensable use of a mask. If the patient is suspicious, he must keep him in a separate area and prioritize his care. Conclusion: The main guidelines that should exist in the outpatient flow to cancer patients were observed, due to the need to reassess the priorities of care and reorganize work logistics, with the pandemic of COVID-19. (AU)

Objetivo: Analizar cambios en el flujo de atención al paciente oncológico, ante la pandemia COVID-19. Métodos: Se trata de una investigación documental en un ambulatorio privado de Aracaju, que incluye lineamientos de las bases de datos provistas por el Ministerio de Salud, el Instituto Nacional del Cáncer y el Departamento de Computación del SUS (DATASUS), referido al SubSistema de Información Hospitalaria. (SIH), así como datos del Sistema de Información Ambulatoria del SUS (SIA-SUS), un módulo de alta complejidad para la atención del cáncer (APAC / ONCO). Resultados: El flujo de pacientes a la entrada de la clínica comienza con la identificación de signos del síndrome gripal. Después de la higiene de las manos y la medición de la temperatura, hay una dirección a otro ambiente con una distancia mínima de 1 metro entre personas, sobre el uso indispensable de una máscara. Si el paciente sospecha, debe mantenerlo en un área separada y priorizar su atención. Conclusión: Se observaron las principales pautas que deben existir en el flujo ambulatorio a pacientes oncológicos, debido a la necesidad de reevaluar las prioridades de atención y reorganizar la logística del trabajo, con la pandemia de COVID-19. (AU)

Infection Biomarkers Based on Metabolomics.

Current infection biomarkers are highly limited since they have low capability to predict infection in the presence of confounding processes such as in non-infectious inflammatory processes, low capability to predict disease outcomes and have limited applications to guide and evaluate therapeutic regimes. Therefore, it is critical to discover and develop new and effective clinical infection biomarkers, especially applicable in patients at risk of developing severe illness and critically ill patients. Ideal biomarkers would effectively help physicians with better patient management, leading to a decrease of severe outcomes, personalize therapies, minimize antibiotics overuse and hospitalization time, and significantly improve patient survival. Metabolomics, by providing a direct insight into the functional metabolic outcome of an organism, presents a highly appealing strategy to discover these biomarkers. The present work reviews the desired main characteristics of infection biomarkers, the main metabolomics strategies to discover these biomarkers and the next steps for developing the area towards effective clinical biomarkers.

Incidental finding of accessory mitral valve tissue on routine adult echocardiography.

Accessory mitral valve tissue is a rare congenital cardiac abnormality that sometimes can cause left ventricular outflow tract obstruction. We herein present the case of a 55-year-old male with an incidental finding of accessory mitral valve tissue on transthoracic echocardiography. The patient was managed conservatively as accessory tissue was not causing left ventricular outflow obstruction and there were no hemodynamic consequences.

Alterações Dermatológicas Associadas ao Tratamento Oncológico de Mulheres com Câncer de Mama / Dermatological Alterations Associated with Oncological Treatment of Women with Breast Cancer / Alteraciones Dermatológicas Asociadas con el Tratamiento Oncológico de Mujeres con Cáncer de Mama

Introdução: Diversos efeitos colaterais podem acometer a pele e seus anexos durante o tratamento oncológico de mulheres com câncer de mama, comprometendo a terapia. Objetivo: Identificar a ocorrência de alterações dermatológicas durante o tratamento oncológico de mulheres com câncer de mama. Método: Estudo documental e retrospectivo, de cunho quantitativo, com uso de dados secundários obtidos por meio de 190 prontuários clínicos (n=190) de um serviço privado de oncologia. Resultados: As participantes apresentaram média de idade de 53 anos (±11,2), com diagnóstico histopatológico de carcinoma ductal invasivo (85,8%). Todas foram submetidas à quimioterapia, 65,3% à mastectomia radical e 34,2% à radioterapia. As alterações dermatológicas identificadas e as ocorrências verificadas na amostra foram alopecia (94,2%), hiperpigmentação (48,4%), prurido (36,3%), eritema (6,8%), descamação (25,8%) e alterações ungueais (77,9%). Ao todo, foram identificadas 550 alterações dermatológicas, resultando em uma média de 2,9 (±1,3) por paciente. A radioterapia esteve associada a uma maior ocorrência de eritema (p<0,001) e mulheres expostas a taxanos apresentaram maior probabilidade de manifestar de alterações dermatológicas do que as não expostas (p<0,001), bem como fatores sociodemográficos não estiveram associados. Conclusão: A ocorrência de alterações dermatológicas identificadas nas participantes foi significativa, reforçando que essas manifestações podem ser frequentes em mulheres com câncer de mama durante o tratamento oncológico, requerendo medidas de prevenção e tratamento.

Introduction: Several side effects can affect the skin and its attachments during cancer treatment of women with breast cancer, compromising the therapy. Objective: To identify the occurrence of dermatological changes during cancer treatment of women with breast cancer. Method:Quantitative approach, documentary and retrospective study, using secondary data obtained from 190 clinical records (n=190) from a private oncology service. Results: The participants had a mean age of 53 years (±11.2), with histopathological diagnosis of invasive ductal carcinoma (85.8%). All participants were exposed to chemotherapy, 65.3% to radical mastectomy and 34.2% to radiotherapy. The dermatological alterations identified, and the occurrences verified in the sample were alopecia (94.2%), hyperpigmentation (48.4%), pruritus (36.3%), erythema (6.8%), desquamation (25.8%) and nail alterations (77.9%). In all, 550 dermatological alterations were identified, resulting in an average of 2.9 (±1.3) changes per patient. Radiotherapy was associated with a higher occurrence of erythema (p<0.001) and women exposed to taxanes were more likely to manifest dermatological alterations than those unexposed (p<0.001), sociodemographic factors were not associated. Conclusion: The occurrence of dermatological alterations identified in the participants was significant, reinforcing that these manifestations may be frequent in women with breast cancer during oncological treatment, requiring prevention and treatment actions.

Introducción: Varios efectos secundarios pueden afectar la piel y sus uniones durante el tratamiento del cáncer de mujeres con cáncer de mama, comprometiendo la terapia. Objetivo: Identificar la aparición de alteraciones dermatológicas durante el tratamiento del cáncer de mujeres con cáncer de mama. Método: Estudio documental y retrospectivo, de carácter cuantitativo, utilizando datos secundarios obtenidos de 190 registros clínicos (n=190) de un servicio oncológico privado. Resultados: Los participantes tenían una edad media de 53 años (±11,2), con diagnóstico histopatológico de carcinoma ductal invasivo (85,8%). Todas fueran sometidas a quimioterapia, el 65,3% a mastectomía radical y el 34,2% a radioterapia. Las alteraciones dermatológicas identificadas y las ocurrencias verificadas en la muestra fueron alopecia (94,2%), hiperpigmentación (48,4%), prurito (36,3%), eritema (6,8%), descamación (25,8%) y alteraciones en las uñas (77,9%). En total, se identificaron 550 alteraciones dermatológicas, lo que resultó en un promedio de 2,9 (±1,3) por paciente. En total, se identificaron 550 cambios dermatológicos, lo que resultó en un promedio de 2,9 (±1,3) alteraciones por paciente. La radioterapia se asoció con una mayor incidencia de eritema (p<0,001) y las mujeres expuestas a taxanos tienen más probabilidades de manifestar alteraciones dermatológicas que las no expuestas (p<0,001), además de que no se asociaron factores sociodemográficos. Conclusión: La ocurrencia de alteraciones dermatológicas identificadas en las participantes fue significativa, reforzando que estas manifestaciones pueden ser frecuentes en mujeres con cáncer de mama durante el tratamiento oncológico, requiriendo acciones de prevención y tratamiento.

On coefficients of Poincaré series and single-valued periods of modular forms.

We prove that the field generated by the Fourier coefficients of weakly holomorphic Poincaré series of a given level Γ 0 ( N ) and integral weight k ≥ 2 coincides with the field generated by the single-valued periods of a certain motive attached to Γ 0 ( N ) . This clarifies the arithmetic nature of such Fourier coefficients and generalises previous formulas of Brown and Acres-Broadhurst giving explicit series expansions for the single-valued periods of some modular forms. Our proof is based on Bringmann-Ono's construction of harmonic lifts of Poincaré series.

Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1.

While endothelial cell (EC) function is influenced by mitochondrial metabolism, the role of mitochondrial dynamics in angiogenesis, the formation of new blood vessels from existing vasculature, is unknown. Here we show that the inner mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis. In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Endothelial Opa1 is indeed required in an NFκB-dependent pathway essential for developmental and tumor angiogenesis, impacting tumor growth and metastatization. A first-in-class small molecule-specific OPA1 inhibitor confirms that EC Opa1 can be pharmacologically targeted to curtail tumor growth. Our data identify Opa1 as a crucial component of physiological and tumor angiogenesis.

Reações adversas em pacientes oncológicos após tratamento radioterápico / Adverse reactions in oncological patients after radiotherapy treatment

Objetivo: Descrever reações adversas após tratamento radioterápico em pessoas com câncer atendidas em um ambulatório de radioterapia. Metodologia: Trata-se de um estudo documental por meio da coleta de dados em prontuários clínicos. Foram avaliados 436 pacientes que realizaram tratamento radioterápico em busca de episódios de reações adversas registrados nos prontuários. Foram elegíveis os pacientes maiores de 18 anos com diagnóstico de neoplasia (confirmado por laudos citopatológicos e/ou histopatológico) que realizaram cinco ou mais sessões de radioterapia entre 2015 e 2016. Resultados: 353 prontuários clínicos foram incluídos (83,6%) e 1.390 reações associadas ao tratamento radioterápico foram descritas nestes pacientes, sendo 53,2% mulheres. As reações adversas mais frequentes relacionadas à radioterapia foram dor (14%), radiodermite (9%) e falta de apetite (8%). 69% dos pacientes não apresentavam sinais ou sintomas antes do diagnóstico, sendo 25% diagnosticados com adenocarcinoma. A técnica de radioterapia mais utilizada foi a 3D (67%), com cerca de 30 frações (14%) e 5000 Gy como dose total planejada (17%). 70% dos pacientes que apresentaram reações adversas possuíam ao menos uma comorbidade. Conclusão: A radioterapia pode estar associada à diversas reações adversas, variando os sinais e sintomas nos pacientes acometidos. A prevenção e o manejo destas condições podem potencializar o tratamento, reduzindo a morbidade e a mortalidade, além de proporcionar qualidade de vida aos pacientes com câncer.

Objective: To describe adverse reactions after radiotherapy treatment in cancer patients treated at a radiotherapy outpatient service. Method: It is a documentary study through the collection of data in clinical records. 436 patients who underwent radiotherapy treatment were evaluated in search of episodes of adverse reactions. Patients over 18 years of age diagnosed with neoplasia (confirmed by cytopathological and/or histopathological reports) who underwent five or more radiotherapy sessions between 2015 and 2016 were eligible. Results: 353 clinical records were included (83.6%) and 1,390 reactions associated with radiotherapy were described in these patients, being 53.2% women. The most frequent adverse reactions related to radiotherapy were pain (14%), radiodermatitis (9%) and poor appetite (8%). 69% of patients had no signs or symptoms before diagnosis, 25% being diagnosed with adenocarcinoma. The most used radiotherapy technique was 3D (67%), with about 30 fractions (14%) and 5000 Gy as the total planned dose (17%). 70% of patients who experienced adverse reactions had at least one comorbidity. Conclusion: Radiotherapy can be associated with several adverse reactions, with different signs and symptoms in affected patients. The prevention and management of these conditions can enhance treatment, reducing morbidity and mortality, in addition to providing quality of life to cancer patients.